Drotaverin hydrochloride

Absorption

Drotaverine is not completely absorbed following oral administration and its bioavailability is highly variable. Following oral administration of a single 80 mg dose, the absolute bioavailability ranged between 24.5 and 91 % with a mean of 58.2 ± 18.2%. Mean Cmax was 292 ± 88 ng/mL. Mean AUC was 3251 ± 950 ng*h/mL. Mean Tmax was 1.9 ± 0.54 hours.

Toxicity

Oral LD50 is 540 mg/kg in rats and 350 mg/kg in mice. There is limited information on drotaverine overdose and toxicity.

Background

Drotaverine is an antispasmodic drug that works by inhibiting phosphodiesterase-4 (PDE4). It is a benzylisoquinoline derivative that is structurally related to papaverine, although it displays more potent antispasmodic activities than papaverine. Drotaverine has been used in the symptomatic treatment of various spastic conditions, such as gastrointestinal diseases, biliary dyskinesia, and vasomotor diseases associated with smooth muscle spasms. It also has been investigated in dysmenorrhea, abortion, and augmentation of labour. More recently, drotaverine gained attention in the treatment of benign prostatic hyperplasia, parainfluenza, and avian influenza viruses.
Drotaverine is not approved by the FDA, European Medicines Agency, or Health Canada. It is approved for use in Thailand as oral tablets or intramuscular injections.

Indications

Drotaverine is used to alleviate gastrointestinal and genitourinary smooth muscle spasms, such as cholecystitis and gallbladder disorders.

Definition

ChEBI: Drotaverine is a member of isoquinolines.

Pharmacokinetics

Drotaverine is an e spasmolytic agent with a relaxing effect on smooth muscles. It works to relieve visceral spasms and improve cervical dilation. In vitro, drotaverine mediated cytostatic effects on several human tumor cell lines and nonmalignant mouse fibroblasts. Drotaverine may have minor allosteric calcium channel blocking properties: in vitro, drotaverine behaves like voltage-dependent L-type calcium channel blockers.

Metabolism

Drotaverine is reported to undergo extensive hepatic metabolism, which is its main route of elimination. It may also undergo biliary excretion to form conjugated metabolites. Proposed metabolic pathways and metabolites are based on limited animal studies: in rats, the major identified metabolites of drotaverine are 4'-desethyl-drotaverine, 6-desethyl-drotaverine, drotaveraldine, and 4'-desethyl-drotaveraldine, all of which are glucuronidated in the bile. 4'-desethyl-drotaveraldine was the most predominant metabolite eliminated into the bile.